Assess effect of predominant polarity on efficacy of cariprazine in patients with bipolar I (BP-I) disorder. Predominant polarity may be an important clinical consideration in BP-I disorder, with predominant depressive episodes associated with delayed diagnosis and higher rates of suicidality, while predominant manic episodes are associated with younger onset, manic/psychotic first episode, and more substance abuse [1].

Data were pooled from 3 randomized, double-blind, cariprazine trials in BP-I depression and 3 trials in BP-I mania. Post hoc analyses were performed in subgroups from the bipolar depression studies with/without predominant depression (≥2:1 ratio of prior lifetime depressive to manic episodes), and in subgroups from the bipolar mania studies with and without predominant mania (≥2:1 ratio of prior lifetime manic to depressive episodes). Change from baseline to week 6 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score was evaluated for cariprazine 1.5 and 3 mg/d versus placebo (bipolar depression studies); change from baseline to week 3 in Young Mania Rating Scale total score was evaluated for cariprazine 3-12 mg/d versus placebo (bipolar mania studies). Change from baseline analyzed using mixed-effect model for repeated measures in pooled intent-to-treat population from each indication.

In bipolar depression studies, there were 624 patients (45% of total study population) in the predominantly depressive subgroup (placebo=197, cariprazine: 1.5 mg/d=217; 3 mg/d=210) and 750 patients (55%) in the subgroup without predominant depression (placebo=258, cariprazine: 1.5 mg/d=241; 3 mg/d=251). In the predominant depressive subgroup, LSMDs for MADRS total score change from baseline were significant versus placebo for cariprazine 1.5 mg/d (-2.49 [-4.30, -.68], P=.0071) and 3 mg/d (-2.48 [-4.31, -.65], P=.0079); in the subgroup without predominant depression, LSMDs were also significant versus placebo for both doses (1.5 mg/d=-3.30 [-5.06, -1.54], P=.0002; 3 mg/d=-2.53 [-4.29, -.77], P=.0049). In bipolar mania studies, there were 721 patients (73% of total study population) in the predominantly manic episode subgroup (placebo=307, cariprazine 3-12 mg/d =414) and 267 patients (27%) in the subgroup without predominant manic episodes (placebo=102, cariprazine 3-12 mg/d=165). In predominant mania subgroup, LSMD in YMRS total score change from baseline was significant for cariprazine 3-12 mg/d versus placebo (-4.65 [-6.29, -3.02], P<.0001); in subgroup without predominant mania, the LSMD for cariprazine versus placebo was also significant (-7.56 [-10.30, -4.82], P<.0001).

Cariprazine was efficacious in treating BP-I mood episodes regardless of predominant polarity for the presenting mood episode. Cariprazine was effective against symptoms of depression in patients with BP-I depression with/without predominant depressive episodes, and against symptoms of mania in patients with BP-I mania with/ without predominant manic episodes.

AbbVie

This data was previously presented at the Annual ECNP Congress; Barcelona, Spain; October 7-10, 2023.